Association analysis identifies 65 new breast cancer risk loci

Since the first reports in 2009, genome-wide association studies (GWAS) have been successful in identifying germline variants associated with glioma susceptibility. In this review, we describe a chronological history of glioma GWAS, culminating in the most recent study comprising 12,496 cases and 18,190 controls. We additionally summarize associations at the 27 glioma-risk SNPs that have been reported so far. Future efforts are likely to be principally focused on assessing association of germline-risk SNPs with particular molecular subgroups of glioma, as well as investigating the functional basis of the risk loci in tumor formation. These ongoing studies will be important to maximize the impact of research into glioma susceptibility, both in terms of insight into tumor etiology as well as opportunities for clinical translation.

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“…72; rs2284063), breast cancer (ref. 116; rs738321), bladder cancer (ref. 117; rs1014971), and multiple myeloma (ref.…”

Section: Chronological History Of Glioma Risk Loci Discoverymentioning

confidence: 99%

Genome-Wide Association Studies in Glioma

Kinnersley

Houlston

Bondy

2018

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Elsewhere, we report 65 new susceptibility loci for overall breast cancer 1 . Three of these are located within 500 kb of the new susceptibility loci for ER-negative disease reported here (variants rs200648189 (2p23.3), rs6569648 (6q23.1) and rs17350191 (8q24.13)).…”

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confidence: 99%

“… Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease 1 . We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin.…”

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confidence: 99%

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Milne¹,

Kuchenbaecker²,

Michailidou³

et al. 2017

Nat Genet

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338

332

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Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10−8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 14% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

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“…1,3 Large-scale genotyping studies have also led to the identification of numerous low risk variants, predominantly consisting of single nucleotide polymorphisms in non-coding sequences. 4,5 Inherited mutations in other genes, such as RAD51C, RAD51D and BRIP1, and mismatch-repair (MMR) genes ( MLH1, MSH2, MSH6, PMS2, EPCAM ) that cause Lynch syndrome when mutated, also influence the risk of ovarian cancer. 6 These genetic discoveries have occurred alongside major advances in sequencing technology that has led to the introduction in the clinic of simultaneous testing of panels of selected multiple genes for hereditary breast and ovarian cancer predisposition.…”

Section: Introductionmentioning

confidence: 99%